Chlamydia infections are a major cause of sexually transmitted disease in the US. Greater understanding of protective immunity to Chlamydia at mucosal surfaces is urgently required if an effective vaccine is to become a reality. This application proposes to develop a TCR transgenic mouse to uncover fundamental aspects of mucosal CD4 T cell biology during infection of the reproductive tract with Chlamydia. Our experimental approach is unique in that it will utilize a natural route of infection, an establishe mouse model of infection where CD4 T cells participate in pathogen clearance, and involve direct visualization of pathogen-specific CD4 T cells using reagents and techniques that we will develop. Our application specifically proposes to, (i) identify antigen presenting cell subsets tha drive CD4 T effector cell priming in the reproductive tract, and (ii) define the heterogeneity of te CD4 T cell memory pool required for protective immunity in the upper reproductive tract. Understanding both these issues will be vitally important for the generation of a vaccine against Chlamydia, one of the most important pathogens affecting the reproductive health of young women in the US.